Mild Cognitive Impairment
Conditions
Brief summary
Elderly humans have an increased risk of dementia which begins as mild defects in memory called mild cognitive impairment. Glutathione (GSH), a key endogenous antioxidant has been linked to cognition. This exploratory study will investigate mechanisms linked to GSH for cognitive impairment (and improvement) by studying humans with mild cognitive impairment who will be evaluated 12-weeks after receiving either N-acetylcysteine and glycine (GSH precursors), or receiving alanine, and a further 12-weeks after stopping these supplements.
Detailed description
Subjects with MCI will be recruited by written informed consent using forms approved by the Baylor IRB. Subjects will stop nonvitamin supplements for 4wks before screening labs (blood count, HbA1c, glucose, lipid profile, liver profile, blood urea nitrogen, Creatinine, thyroid stimulating hormone, free T4), and for the entire 24wks duration of the study. 60 fasted subjects will have the following measures before and after 12wks of supplementation with cysteine (as N-acetylcysteine) plus glycine vs alanine: (1) Cognitive function using ADCS-PACC (Alzheimer's Disease Co-operative Study-Preclinical Alzheimer's Cognitive Composite which includes Free and Cued Selective Reminding Test, Immediate and Delayed paragraph recall score, Digit-Symbol Substitution Test, Mini mental state examination; (2) Red-cell concentrations of GSH, cysteine, glycine, glutamic acid; plasma malondialdehyde, F2/F3-isoprostanes, sICAM, sVCAM, E-selectin; endothelial function; (3) Mitochondrial glucose oxidation by calorimetry. Measures will be repeated for washout effects 12-wks after stopping supplements.
Interventions
DIETARY_SUPPLEMENTGlycine
Dietary Supplement: glycine will be supplemented in the active arm for 12-weeks
DIETARY_SUPPLEMENTN-acetylcysteine (NAC)
Dietary Supplement: NAC will be supplemented in the active arm for 12-weeks
DIETARY_SUPPLEMENTAlanine
Dietary Supplement: Alanine will be supplemented in the placebo arm for 12-weeks
Sponsors
Baylor College of Medicine
The Methodist Hospital Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
at study entry: (1) Diagnosis of Mild Cognitive Impairment
Exclusion criteria
at study entry: (1) hospitalization within past 3 months; (2) known diabetes; (3) creatinine greater than or equal to 1.5 mg/dL; (4) hemoglobin concentration less than 11 g/dL; (5) known liver disease, or AST/ALT greater than or equal to 2x ULN; (6) history of stroke, brain tumor, or active heart failure; (7) history of psychiatric disorders; (8) untreated depression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cognition | Change between 0-weeks and 12-weeks | Measured using ADCS-PACC |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of Glutathione | Change between 0-weeks and 12-weeks | Measured in red cells |
| Concentrations of TBARS, F2,F3 isoprostanes | Change between 0-weeks and 12-weeks | Measured in plasma |
| Endothelial function markers sICAM, sVCAM, E-selectin | Change between 0-weeks and 12-weeks | Measured in plasma |
| Endothelial function | Change between 0-weeks and 12-weeks | Measured using the EndoPAT system |
| Mitochondrial fuel oxidation in fasted and fed states | Change between 0-weeks and 12-weeks | Measured using calorimetry |
| Insulin resistance | Change between 0-weeks and 12-weeks | Measured as HOMA-IR |
Countries
United States
Outcome results
None listed