Evaluation of the Efficacy of Varenicline on Cognition, Safety, Tolerability and Pharmacokinetics in Subjects With Mild-to-Moderate Alzheimer's Disease

1. Assess the efficacy of varenicline, relative to placebo, on a performance based measure of cognition in patients with mild to moderate Alzheimer's disease
2. Evaluate the effects of varenicline on clinically relevant measures including attention and executive function, behavior, and clinician rated global change.
3. Evaluate the safety and tolerability of varenicline, relative to placebo, in patients with mild to moderate Alzheimer's disease
4. Evaluate the pharmacokinetics of varenicline in patients with mild to moderate Alzheimer's disease.

• Drug: Varenicline
  0.5 mg once daily for 1 week followed by 0.5 mg twice daily for 1 week followed by 1 mg twice daily for 4 weeks
  Other Name: Chantix, Champix
• Drug: Placebo
  Placebo once daily for 1 week followed by placebo twice daily for 5 weeks.

• Experimental: Varenicline
  Intervention: Drug: Varenicline
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Males or females, age 55-85
• Diagnosis of probable Alzheimer's disease, consistent with criteria from both: 1) National Institute of Neurological and Communicable Disease and Stroke and Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) and 2) Diagnostic and Statistical Manual of Mental Disorders (DSM IV)
• Mini-mental status exam score of 14-26 inclusive
• Rosen-Modified Hachinski Ischemia Score of < or = 4

Exclusion Criteria:

• Diagnosis or history of other dementia or neurodegenerative disorders
• Diagnosis or history of clinically significant cerebrovascular or cardiovascular disease
• Subjects with pulmonary disease or evidence of clinically significant pulmonary symptoms