A Pilot of the Feasibility of Using the Iron-Chelator Deferiprone on Mild Cognitive Impairment

The investigators propose to conduct a series of N of One (No1) single blinded clinical trials to pilot the feasibility of using the iron-chelator deferiprone on Mild Cognitive Impairment (MCI). Chelation therapy has previously been reported to slow the rate of cognitive decline in Alzheimer's Disease (AD) by 50% in a single human randomized clinical trial.

Iron chelation's mechanism of action (MOA) in Alzheimer's disease (AD) is uncertain. Potential MOA include reversal of aluminum (AL) toxicity, the prevention of a-beta aggregation, β-amyloid disaggregation, and the obstruction of microbacterial and viral parasitism. The latter mechanism involves augmentation of innate immunity, and disruption of microbacterial iron metabolism. Infectious models of AD's pathophysiology have been recently proposed. Iron blocks toll-like receptor (TLR) initiated anti-microbial actions mediated via gamma-interferon (IFN-γ) tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-10 (IL-10). These biomarkers are of interest because they have also been associated with our novel latent dementia phenotype (i.e., "d" for "dementia") in the Texas Alzheimer's Research and Care Consortium (TARCC). "d" is a continuous measure of dementia severity that can be constructed from any cognitive battery that also includes a measure of Instrumental Activities of Daily Living (IADL). Serum biomarkers might "trigger" dementing processes without participating in their later stages. Thus, the investigators have indications as to who might benefit from iron-chelation and when the intervention might be best applied. This knowledge may help them detect an effect of deferiprone on prospective change in "d" and even on MCI conversion in TARCC NHW (Non Hispanic White) subjects.

Eligibility Criteria:
Inclusion Criteria:

1. MA (Mexican Americans) or NHW TARCC participants with competent informants;
2. TARCC diagnosis of "MCI" (any subtype);
3. Incident MCI or conversion to MCI from control in the two previous TARCC waves;
4. 65-80 yrs of age;
5. Non-institutionalized level of care;
6. Capacity to give informed consent
7. GDS (Geriatric Depression Screen) score (15 item) ≤ 6;
8. TARCC MMSE (Mini-Mental State Examination) ≥ 26 /30;
9. HIS (Hachinski Ischemic Scale) ≤ 05/15;
10. Most recent TARCC dEQ-score = 0 ± 0.25.

Exclusion Criteria:

1. A clinical diagnosis of "Diabetes Mellitus" and current treatment with insulin;
2. A self-reported diagnosis of "Major Depression" (treatment with "antidepressants" not exclusionary);
3. A history of psychosis, including visual hallucinations;
4. History or treatment for Parkinson's, or tremor, or Rapid Eye Movement (REM) behavior disorder;
5. History or treatment for atrial fibrillation;
6. Treatment for cancer in the last 5 years (exc. skin cancers);
7. Major surgery in the last year;
8. History of craniotomy;
9. Serum Ferritin \< 500mcg/ml, Hgb \< 14g/dl♂ /12g/dl♀,, HCT \< 45%♂ /40%♀, recent blood transfusion (last 5 years), FeSO4 supplementation, erythromycin therapy;
10. ANC (absolute neutrophil count) \< 500 cells/µL, platelet count \< 150 × 106 /ml;
11. Treatment with anti-convulsants, mood stabilizers, neuroleptics, opiates, muscle relaxants, systemic steroids, or AD-indicated agents.