Glutathione in Mild Cognitive Impairment

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.

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.