Metformin in Amnestic Mild Cognitive Impairment (MCI)

Inclusion Criteria:

• Age range: 55 to 90 years;
• Sex distribution: men and women;
• Languages: fluent in English or Spanish.

• Subjects must score below a pre-determined cut-off score on the logical memory II delayed paragraph recall sub-test of the Wechsler Memory Scale Revised (WMS-R)26:

  1. less than or equal to 8 for 16 or more years of education.;
  2. less than or equal to 4 for 8-15 years of education;
  3. less than or equal to 2 for 0-7 years of education.
• Global Clinical dementia rating (CDR) score must be 0.5 at screening. The memory box score must be 0.5 or 1.0, with no more than two box scores other than memory rated as high as 1.0 and no box score rated greater than 1.0.
• Subjects without a known history of diabetes or diabetes that has never been treated with medications. If diabetes is diagnosed during screening or they have a history of diabetes not treated in the last 12 months they will be excluded if their HbA1c is > 6.5.
• BMI ≥ 25 kg/m2
• No contraindications to metformin treatment.
• General cognition and functional performance such that a diagnosis of dementia cannot be made at the time of screening based on DSM-IV criteria.
• Vision and hearing must be sufficient for compliance with testing procedures.

Exclusion Criteria:

• Subjects with uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 95 mmHg;
• Subjects with a history of active cancer or cancer within last five years, with the exception of squamous or basal cell carcinoma of the skin;
• Subjects who for any reason may not complete the study as judged by the study physician;
• Abnormal TSH, B12, and RPR.
• Contraindications to metformin use include a creatinine of > 1.5, liver disease by history or by elevated transaminases, congestive heart failure, and alcohol abuse.
• We will also exclude subjects with a history of intolerance to metformin.