This proposal aims to determine whether low does of the alpha-2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated cognitive functions in healthy elderly subjects.

Primary:

• To determine whether low does of the α2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated working memory and executive control functions, in healthy elderly subjects. Subjects will be randomly assigned to receive placebo or guanfacine at one of two dose levels: 0.1 mg, or 0.5 mg daily at bedtime in double-blind fashion for twelve weeks.

Secondary:

• To determine whether guanfacine can favorably influence global status and quality of life (QOL) in healthy elderly subjects.
• To determine whether low-dose guanfacine is safe and well-tolerated in healthy elderly subjects.

Inclusion Criteria:

Subjects enrolled will be nondemented, male and female individuals who meet the following inclusion criteria:

• 75 years of age or older
• Fluent in English
• Stable medical condition for at least 4 weeks prior to Screening visit
• Stable dose of non-excluded medications for at least 4 weeks prior to Screening visit

Exclusion Criteria:

• Dementia
• Mild Cognitive Impairment (Amnestic MCI)
• Clinically significant neurologic disease
• Clinically significant or unstable medical conditions that would interfere with participation in the trial
• Known hypersensitivity to guanfacine
• History of alcohol or substance abuse or dependence within the past 5 years
• Active major psychiatric disorders, including major depression
• History of mental retardation
• Significant abnormalities on clinical laboratories, ECG, or physical examination
• Impairment of visual or auditory acuity sufficient to interfere with completion of study procedures
• Education level < 6 years

The baseline population consists of the 123 participants (out of 154) that met eligibility requirements and consented to participate in the study.