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

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.

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.